Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2
| Authors | |
|---|---|
| Year of publication | 2023 |
| Type | Article in Periodical |
| Magazine / Source | Science Advances |
| MU Faculty or unit | |
| Citation | |
| web | https://www.science.org/doi/10.1126/sciadv.adh9673 |
| Doi | http://dx.doi.org/10.1126/sciadv.adh9673 |
| Keywords | CONVERGENT EXTENSION; WNT/BETA-CATENIN; ENDOCYTOSIS; RECEPTORS; PROTEINS; ACTIVATION; GROWTH; LGR5; RHO |
| Attached files | |
| Description | The mammalian intestine is one of the most rapidly self-renewing tissues, driven by stem cells residing at the crypt bottom. Paneth cells form a major element of the niche microenvironment providing various growth factors to orchestrate intestinal stem cell homeostasis, such as Wnt3. Different Wnt ligands can selectively activate ß-catenin–dependent (canonical) or –independent (noncanonical) signaling. Here, we report that the Dishevelled-associated activator of morphogenesis 1 (Daam1) and its paralogue Daam2 asymmetrically regulate canonical and noncanonical Wnt (Wnt/PCP) signaling. Daam1/2 interacts with the Wnt inhibitor RNF43, and Daam1/2 double knockout stimulates canonical Wnt signaling by preventing RNF43-dependent degradation of the Wnt receptor, Frizzled (Fzd). Single-cell RNA sequencing analysis revealed that Paneth cell differentiation is impaired by Daam1/2 depletion because of defective Wnt/PCP signaling. Together, we identified Daam1/2 as an unexpected hub molecule coordinating both canonical and noncanonical Wnt, which is fundamental for specifying an adequate number of Paneth cells. |
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